Accounting for Biological Sex and Gender Identity in the Pathogenesis, Artistic Depictions, and Quality of Life in Neurofibromatosis Type 1

Abstract

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous syndrome caused by pathogenic alterations in the tumor suppressor protein neurofibromin. NF1 is characterized clinically by café-au-lait macules, skinfold freckling, iris hamartomas, benign and malignant nerve sheath tumors, optic pathway tumors, skeletal abnormalities, breast malignancies, and neurocognitive challenges. Although progress has been made in understanding biological sex- and gender identity–based differences in a variety of dermatologic conditions, the role of these factors on NF1 and vice versa is not well-defined. In this narrative review, we examine the reciprocal influences of biological sex and gender identity on various NF1 clinical features, discuss the psychosocial and sociocultural factors that may contribute to these observed effects, and highlight historical artistic depictions of NF1. We also identify gaps in our current knowledge in this area that warrant additional research. A comprehensive understanding of NF1 clinical presentations through the lens of biological sex and gender identity can lead to a patient-centered approach of treatment, thereby improving long-term outcomes for affected patients.